With growing global desalination capacity, brine from desalination plants has become an environmental threat to the ecosystems. One sustainable method for brine treatment is to develop zero liquid discharge systems that completely convert seawater into freshwater and salts. This paper presents a zero liquid discharge system, which consists of multi-effect distillation and evaporative crystallization, to treat desalination brine with a salinity of 70 g/kg. A thermodynamic analysis is firstly conducted for the proposed system. The specific heat consumption, specific heat transfer area, and Second-law efficiency are found to be 600–1100 kJ/kg, 110–340 m2/(kg/s), and 10–17%, respectively. The heat consumption can be effectively reduced by increasing the number of MED stages, while the specific heat transfer area decreases significantly with higher heat source temperatures. Based on the thermodynamic performance, a techno-economic analysis is conducted for the proposed system, and the specific cost is calculated to be $4.17/m3. Cost reduction can be achieved via employing cost-effective heat sources, reducing heat consumption, and scaling up the system. By selling the freshwater and salt crystals, the system will be more competitive than other existing brine treatment methods.